2012 – Page 2 – American ME and CFS Society

Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit

Abstract:

We report on an audit of 138 ME/CFS patients who attended a private practice and took the ATP Profile biomedical test. The results revealed that all of these patients had measureable mitochondrial dysfunction. A basic treatment regime, based on 1) eating the evolutionary correct stone-age diet, 2) ensuring optimum hours of good quality sleep, 3) taking a standard package of nutritional supplements, and 4) getting the right balance between work and rest, was recommended for all patients. Additions to the basic regime were tailored for each patient according to the results of the ATP Profile and additional nutritional tests and clues from the clinical history.

Mitochondrial function is typically impaired in two ways: substrate or co-factor deficiency, and inhibition by chemicals, exogenous or endogenous. For the former, additional nutrients are recommended where there is a deficiency, and for the latter, improvement of anti-oxidant status and selective chelation therapy or far-infrared saunas are appropriate. We show case histories of nine patients who have taken the ATP Profile on three or four occasions, and a before-and-after treatment summary of the 34 patients who have had at least two ATP Profile tests separated by some months.

Finally, we summarize the results for the 30 patients who followed all aspects of the treatment regime and compare them with the 4 patients who were lax on two or more aspects of the treatment regime. All patients who followed the treatment regime improved in mitochondrial function by on average a factor of 4.

Source: Myhill S, Booth NE, McLaren-Howard J. Targeting mitochondrial dysfunction in the treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) – a clinical audit. Int J Clin Exp Med. 2013;6(1):1-15. Epub 2012 Nov 20. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515971/ (Full article)

Implementing evidence-based practice for patients with chronic fatigue syndrome

Abstract:

The aim of our study was to explore whether community-based mental health care centres (MHCs) are able to implement and sustain cognitive behaviour therapy (CBT) for chronic fatigue syndrome (CFS) with the help of an implementation manual. We monitored the implementation process and treatment outcome data of three Dutch MHCs that implemented or sustained CBT for CFS, one in the context of a stepped care programme. We compared these data with findings of other treatment studies conducted in the context of CBT for CFS.

All three MHCs included at least 40 patients with dropout rates between 15% and 35% from intention-to-treat to second assessment. Effect sizes ranged between 0.88 and 1.76 for changes in fatigue severity and 0.43 and 1.23 for changes in physical functioning. With one exception, these outcomes were within the range of our benchmark. Contrary to original expectations, we provided additional implementation support to the two MHCs new with CBT for CFS. We concluded that our implementation manual does not seem to substitute external support for team leaders and associated professions during initial implementation of CBT for CFS but may have the potential to make this assistance more efficient. Particular attention should be paid to challenges of implementing stepped care for CFS.

KEY PRACTITIONERS MESSAGE: Implementation of CBT for CFS in community-based MHCs was monitored. External support was provided in addition to an implementation manual during initial implementation of CBT for CFS. Participating MHCs were generally capable of successfully implementing and delivering CBT for CFS. Implementation of low-intensity interventions for CFS might better be postponed until therapists have sufficient experience with conventional CBT for CFS.

Source: Wiborg JF, Wensing M, Tummers M, Knoop H, Bleijenberg G. Implementing evidence-based practice for patients with chronic fatigue syndrome. Clin Psychol Psychother. 2014 Mar-Apr;21(2):108-14. doi: 10.1002/cpp.1827. Epub 2012 Dec 11. https://www.ncbi.nlm.nih.gov/pubmed/23229956

Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two “fatigue” syndromes with overlapping symptoms and possibly related aetiologies

Abstract:

In July 2010, at the Muscle Fatigue Meeting, I presented an overview of Chronic Fatigue Syndrome and Cancer Related Fatigue, emphasizing a critical interpretation of the potential association between Chronic Fatigue Syndrome and Cancer Related Fatigue and a newly discovered retrovirus: Xenotropic Murine Related Virus. Since this association was hotly debated at that time, I suggested at the Meeting that it was wrong and most likely due to the identification of the wrong virus culprit.

Today, 20 months after the Meeting, the first part of our prediction has turned out to be correct, as Xenotropic Murine Related Virus was shown to be a laboratory-created artefact. Still, the potential association of fatigue-syndromes with an infection (most likely viral) is sustained by a plethora of evidence and this overview will initially summarize data suggesting prior viral infection(s). The principal hypothesized mechanisms for both peripheral and central Chronic Fatigue Syndrome/Cancer Related Fatigue will be then summarized, also indicating plausible associations and triggering factors.

All evidence accrued so far suggests that further research work should be performed in this interesting area and in order to identify an infectious agent for Chronic Fatigue Syndrome/Cancer Related Fatigue. One candidate RNA virus, Micro-Foci inducing Virus, will be described in this overview.

Source: Rovigatti U. Chronic Fatigue Syndrome (CFS) and Cancer Related Fatigue (CRF): two “fatigue” syndromes with overlapping symptoms and possibly related aetiologies. Neuromuscul Disord. 2012 Dec;22 Suppl 3:S235-41. doi: 10.1016/j.nmd.2012.10.018. https://www.ncbi.nlm.nih.gov/pubmed/23182646

Altered immune pathway activity under exercise challenge in Gulf War Illness: an exploratory analysis

Abstract:

Though potentially linked to the basic physiology of stress response we still have no clear understanding of Gulf War Illness (GWI), a debilitating illness presenting with a complex constellation of immune, endocrine and neurological symptoms. Here we compared male GWI (n=20) with healthy veterans (n=22) and subjects with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) (n=7). Blood was drawn during a Graded eXercise Test (GXT) prior to exercise, at peak effort (VO2 max) and 4-h post exercise. Affymetrix HG U133 plus 2.0 microarray gene expression profiling in peripheral blood mononuclear cells (PBMCs) was used to estimate activation of over 500 documented pathways. This was cast against ELISA-based measurement of 16 cytokines in plasma and flow cytometric assessment of lymphocyte populations and cytotoxicity. A 2-way ANOVA corrected for multiple comparisons (q statistic <0.05) indicated significant increases in neuroendocrine-immune signaling and inflammatory activity in GWI, with decreased apoptotic signaling. Conversely, cell cycle progression and immune signaling were broadly subdued in CFS. Partial correlation networks linking pathways with symptom severity via changes in immune cell abundance, function and signaling were constructed.

Central to these were changes in IL-10 and CD2+ cell abundance and their link to two pathway clusters. The first consisted of pathways supporting neuronal development and migration whereas the second was related to androgen-mediated activation of NF-κB. These exploratory results suggest an over-expression of known exercise response mechanisms as well as illness-specific changes that may involve an overlapping stress-potentiated neuro-inflammatory response.

Source: Broderick G, Ben-Hamo R, Vashishtha S, Efroni S, Nathanson L, Barnes Z, Fletcher MA, Klimas N. Altered immune pathway activity under exercise challenge in Gulf War Illness: an exploratory analysis. Brain Behav Immun. 2013 Feb;28:159-69. doi: 10.1016/j.bbi.2012.11.007. Epub 2012 Nov 29. https://www.ncbi.nlm.nih.gov/pubmed/23201588

Lipid and protein oxidation in female patients with chronic fatigue syndrome

Abstract:

INTRODUCTION: Chronic fatigue syndrome (CFS) is a widely recognized problem, characterized by prolonged, debilitating fatigue and a characteristic group of accompanying symptoms, that occurs four times more frequently in women than in men. The aim of the study was to determine the existence of oxidative stress and its possible consequences in female patients with CFS.

MATERIAL AND METHODS: Twenty-four women aged 15-45 who fulfilled the diagnostic criteria for CFS with no comorbidities were recruited and were age matched to a control group of 19 healthy women. After conducting the routine laboratory tests, levels of the lipid oxidation product malondialdehyde (MDA) and protein oxidation protein carbonyl (CO) were determined.

RESULTS: The CFS group had higher levels of triglycerides (p = 0.03), MDA (p = 0.03) and CO (p = 0.002) and lower levels of HDL cholesterol (p = 0.001) than the control group. There were no significant differences in the levels of total protein, total cholesterol or LDL cholesterol.

CONCLUSIONS: The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.

Source: Tomic S, Brkic S, Maric D, Mikic AN. Lipid and protein oxidation in female patients with chronic fatigue syndrome. Arch Med Sci. 2012 Nov 9;8(5):886-91. doi: 10.5114/aoms.2012.31620. Epub 2012 Nov 7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3506242/ (Full article)

Attributions, distress and behavioural responses in the significant others of people with chronic fatigue syndrome

Abstract:

To test an attribution-emotion model of reactions to chronic fatigue syndrome/myalgic encephalomyelitis, 30 significant others of 30 adult patients with chronic fatigue syndrome/myalgic encephalomyelitis were administered a semi-structured interview about their beliefs regarding the patient’s illness and completed questionnaire measures of distress and behavioural responses to the patient. Spontaneous causal explanations (attributions) for illness events, symptom exacerbation and negative patient mood were extracted and coded. Significant others’ distress and negative behavioural responses towards the chronic fatigue syndrome/myalgic encephalomyelitis patient were associated with attributing illness events to causes personal and internal to the patient. Our findings may inform the future family-based interventions for chronic fatigue syndrome/myalgic encephalomyelitis.

Source: Brooks JM, Daglish J, Wearden AJ. Attributions, distress and behavioural responses in the significant others of people with chronic fatigue syndrome. J Health Psychol. 2013 Oct;18(10):1288-95. doi: 10.1177/1359105312464670. Epub 2012 Nov 23. https://www.ncbi.nlm.nih.gov/pubmed/23180874

Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome

Abstract:

BACKGROUND: Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS.

METHODS: Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between-group differences in autonomic reactivity and associations with cognitive performance were analysed.

RESULTS: Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes.

CONCLUSIONS: These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity.

Source: Beaumont A, Burton AR, Lemon J, Bennett BK, Lloyd A, Vollmer-Conna U. Reduced cardiac vagal modulation impacts on cognitive performance in chronic fatigue syndrome. PLoS One. 2012;7(11):e49518. doi: 10.1371/journal.pone.0049518. Epub 2012 Nov 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498107/ (Full article)

Unity of opposites? Chronic fatigue syndrome and the challenge of divergent perspectives in guideline development

Abstract:

Guideline development by its nature is a process and method of integration and synthesis of information, be it originating from research, evidence-based medicine, clinical findings, patient experience and/or individual narratives of an illness or disease. In the majority of cases, it can be assumed that this information and these ideas are travelling in the same direction; however, it is possible that the objective and subjective cannot be synthesised, and appear mutually contradictory.

In this commentary, an example of where this might be the case has been analysed: a report published by the Scottish Public Health Network, a Health Care Needs Assessment of Services for people living with myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS). It appears from reflection and analysis of this document that this process may indeed have gone awry. We propose that, if followed, this document would lead to the adoption of dangerous diagnostic criteria for ME/CFS, as well as preventing patients from making informed decisions about treatment options, and discouraging clinicians from following evidence-based medicine and recommending proven treatments for ME/CFS, because of potential implications for future commissioning. This commentary seeks to highlight some of the problems, contradictions and unintended consequences of a divergence between patient perspectives and evidence-based medicine despite probably sharing the same aim, that of improving patient care and striving for better understanding and better treatments for disease.

Comment in:

Who values evidence? [J Neurol Neurosurg Psychiatry. 2014]

Chronic fatigue syndrome/myalgic encephalomyelitis: more heat, some light–directions for research and clinical practice. [J Neurol Neurosurg Psychiatry. 2014]

Source: Smith C, Wessely S. Unity of opposites? Chronic fatigue syndrome and the challenge of divergent perspectives in guideline development. J Neurol Neurosurg Psychiatry. 2014 Feb;85(2):214-9. doi: 10.1136/jnnp-2012-303208. Epub 2012 Nov 17. https://www.ncbi.nlm.nih.gov/pubmed/23160704

Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset

Abstract:

BACKGROUND: A defined diagnostic panel differentiated patients who had been diagnosed with chronic fatigue syndrome (CFS), based upon Fukuda/Carruthers criteria. This diagnostic panel identified an Epstein-Barr virus (EBV) subset of patients (6), excluding for the first time other similar “clinical” conditions such as cytomegalovirus (CMV), human herpesvirus 6 (HHV6), babesiosis, ehrlichiosis, borreliosis, Mycoplasma pneumoniae, Chlamydia pneumoniae, and adult rheumatic fever, which may be mistakenly called CFS. CFS patients were treated with valacyclovir (14.3 mg/kg q6h) for ≥ 12 months. Each patient improved, based upon the Functional Activity Appraisal: Energy Index Score Healthcare Worker Assessment (EIPS), which is a validated (FSS-9), item scale with high degree of internal consistency measured by Cronbach’s alpha.

METHODS: Antibody to EBV viral capsid antigen (VCA) IgM, EBV Diffuse Early Antigen EA(D), and neutralizing antibodies against EBV-encoded DNA polymerase and EBV-encoded dUTPase were assayed serially approximately every three months for 13-16 months from sera obtained from patients with CFS (6) and from sera obtained from twenty patients who had no history of CFS.

RESULTS: Antibodies to EBV EA(D) and neutralizing antibodies against the encoded-proteins EBV DNA polymerase and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) were present in the EBV subset CFS patients. Of the sera samples obtained from patients with CFS 93.9% were positive for EA(D), while 31.6% of the control patients were positive for EBV EA(D). Serum samples were positive for neutralizing antibodies against the EBV-encoded dUTPase (23/52; 44.2%) and DNA polymerase (41/52; 78.8%) in EBV subset CFS patients, but negative in sera of controls.

CONCLUSIONS: There is prolonged elevated antibody level against the encoded proteins EBV dUTPase and EBV DNA polymerase in a subset of CFS patients, suggesting that this antibody panel could be used to identify these patients, if these preliminary findings are corroborated by studies with a larger number of EBV subset CFS patients.

Source: Lerner AM, Ariza ME, Williams M, Jason L, Beqaj S, Fitzgerald JT, Lemeshow S, Glaser R.Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset. PLoS One. 2012;7(11):e47891. doi: 10.1371/journal.pone.0047891. Epub 2012 Nov 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3498272/ (Full article)

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome

Abstract:

Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101).

Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors. Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity.

To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies. While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B. However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients. These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.

Source: Burbelo PD, Bayat A, Wagner J, Nutman TB, Baraniuk JN, Iadarola MJ. No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome. Am J Transl Res. 2012;4(4):443-51. Epub 2012 Oct 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493030/ (Full article)